{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T23:54:34Z","timestamp":1792194874873,"version":"4.4.0"},"reference-count":47,"publisher":"National Academy of Sciences","issue":"50","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2011,12,13]]},"abstract":"<jats:p>\n                    Human artificial chromosome (HAC)-based vectors offer a promising system for delivery and expression of full-length human genes of any size. HACs avoid the limited cloning capacity, lack of copy number control, and insertional mutagenesis caused by integration into host chromosomes that plague viral vectors. We previously described a synthetic HAC that can be easily eliminated from cell populations by inactivation of its conditional kinetochore. Here, we demonstrate the utility of this HAC, which has a unique gene acceptor site, for delivery of full-length genes and correction of genetic deficiencies in human cells. A battery of functional tests was performed to demonstrate expression of\n                    <jats:italic>NBS1<\/jats:italic>\n                    and\n                    <jats:italic>VHL<\/jats:italic>\n                    genes from the HAC at physiological levels. We also show that phenotypes arising from stable gene expression can be reversed when cells are \u201ccured\u201d of the HAC by inactivating its kinetochore in proliferating cell populations, a feature that provides a control for phenotypic changes attributed to expression of HAC-encoded genes. This generation of human artificial chromosomes should be suitable for studies of gene function and therapeutic applications.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1114483108","type":"journal-article","created":{"date-parts":[[2011,11,29]],"date-time":"2011-11-29T21:43:52Z","timestamp":1322603032000},"page":"20048-20053","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":76,"title":["Human artificial chromosome (HAC) vector with a conditional centromere for correction of genetic deficiencies in human cells"],"prefix":"10.1073","volume":"108","author":[{"given":"Jung-Hyun","family":"Kim","sequence":"first","affiliation":[{"name":"Laboratories of aMolecular Pharmacology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Artem","family":"Kononenko","sequence":"additional","affiliation":[{"name":"Laboratories of aMolecular Pharmacology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Indri","family":"Erliandri","sequence":"additional","affiliation":[{"name":"Laboratories of aMolecular Pharmacology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tae-Aug","family":"Kim","sequence":"additional","affiliation":[{"name":"Tumor and Stem Cell Biology, National Cancer Institute, Bethesda, MD 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megumi","family":"Nakano","sequence":"additional","affiliation":[{"name":"Kazusa DNA Research Institute, Kisarazu, Chiba 292-0818, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuichi","family":"Iida","sequence":"additional","affiliation":[{"name":"Institute of Regenerative Medicine and Biofunction, Tottori University, Tottori 683-8503, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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